Downstream Processing

New Antibody Formats on the Block:
More Complex Modalities Demand Innovation in Manufacturing and Purification

Some of the latest, most promising therapeutic developments in the biologics industry use antibody fragments — either separate functional subunits of antibodies or recombinant molecules that are composed of immunoglobulin domains. The most popular fragments are antigen-binding fragments (Fabs), variable single-chain fragments (scFvs), diabodies, and nanobodies. Such molecules raise several advantages over their parent molecules for upstream production but pose several challenges for downstream purification. To facilitate antibody-fragment capture, Tosoh Bioscience has developed Toyopearl AF-rProtein L-650F resin. Its ligand uses…

PendoTECH Sensors and Industry 4.0: Integrating a PendoTECH Single-Use Sensor System with a Digital Highway

Biopharmaceutical manufacturing is evolving with the progression of Industry 4.0. Industry 4.0 refers to the ongoing “fourth industrial revolution,” which is transforming modern manufacturing and production practices through the use of “smart” technology. This is appealing especially to the biopharmaceutical industry, where production can be a long, meticulous, complex process, and optimizing manufacturing procedures is critical for success. As a leading supplier of single-use technology for the biopharmaceutical industry, PendoTECH recently has explored how its products can be integrated easily…

The iCapTag Protein Purification Platform: Bridging Research and Manufacturing

Purification of recombinant proteins remains a critical challenge for applications ranging from basic biological research to the development and production of lifesaving biopharmaceuticals. At laboratory scales, the rapid purification of large numbers of new and uncharacterized protein targets effectively compels the use of affinity tags, which enable reliable purification using simple, established protocols with minimal optimization. Tags cannot be used for therapeutic applications, however, because of their potential for immunogenicity. Thus, for proteins other than monoclonal antibodies (which typically use…

Achieve Best-in-Class Purification with the Avantor J.T.Baker BAKERBOND PROchievA Resin

There is an established, global pipeline of existing and upcoming monoclonal antibody (MAb) drugs that treat a wide variety of clinical indications. In MAb manufacturing, protein A chromatography is a proven downstream purification process, but there remains a need to reduce total costs while improving purity and yield. The Avantor J.T.Baker BAKERBOND PROchievA recombinant protein A chromatography resin advances the production of MAbs by providing different choices to biopharmaceutical supply chains. Offered both as a bulk resin and as prepackaged…

eBook: Process-Related Impurities — Emerging Strategies for Detection, Identification, and Management of Host-Cell Proteins

Host-cell proteins (HCPs) represent a major class of process-related impurities (PRIs) that are generated during biopharmaceutical manufacture. Although the vast majority of such proteins are removed from a drug substance during downstream purification, residual HCPs can remain in a finished drug product. Even in minimal concentrations, copurifying HCPs can pose safety risks and compromise protein-product yield, efficacy, and stability. Thus, regulatory agencies consider the presence of HCPs to be a critical quality attribute (CQA). Sufficient clearance of these impurities helps…

Ligand-Based Exosome Affinity Purification: A Scalable Solution to Extracellular Vesicle Downstream Bottlenecks

Novel therapeutics based on extracellular vesicles (EVs) recently passed a critical development milestone. During 2020, some of the first experimental EV products developed by biopharmaceutical companies entered human clinical trials (1–3). EVs are nanometer-sized, lipid-wrapped spheres released by almost every cell type in the human body. EVs are loaded with a cargo of proteins, lipids, and RNA, and they are tagged with surface markers that favor uptake by target cells. Thus, EVs are a key mode of cell-to-cell communication (4).…

Validation of a Next-Generation Single-Use Turbidity System

Turbidity describes the relative clarity of a liquid as the result of suspended solids. Instruments that measure turbidity typically use a beam of light to detect particles by measuring the difference between the amount of light emitted from the light source and the amount that is received by a detector. Such measurements are affected by the size, shape, and number of particles in a sample of liquid because those solids scatter the incoming light, which provides an apparent absorbance that…

Eliminating the Analytical Bottleneck in Production and Purification of mRNA

COVID-19 has focused a spotlight on the ability of mRNA technology to accelerate vaccine development and approval (1). That same technology can hasten development and approval of other therapeutic classes, including cancer immunotherapy, protein replacement, and gene therapy. Fulfilling those opportunities imposes significant challenges on process developers and manufacturers to improve existing processes. Scale-up to produce millions of doses (tens of kilograms) compounds those challenges. Furthermore, every step of the journey requires high-performance analytical methods, to ensure patient safety and…

Ask the Expert: Selecting the Right Buffer Management Strategy

Although buffers are among the simplest materials used in bioprocessing, they are critical to biopharmaceutical manufacturing success. Buffer preparation, storage, and handling can require significant investments in time, labor, equipment, and facility space. Jenny Dunker, MSc, and Alexander Troken, PhD (global product managers for customized bioprocess solutions and for process liquids and buffers, respectively, at Cytiva), delivered an “Ask the Expert” presentation on 30 March 2021 to explore strategies for intensifying buffer management. Available Options Biopharmaceutical manufacturers often prepare buffers…

Predicting Viral Clearance in Downstream Process Development

As viruses can arise during the manufacture of biopharmaceuticals, regulatory agencies require viral clearance validation studies for each biopharmaceutical prior to approval. These studies are typically conducted in biosafety level (BSL)-2 facilities and require large capital and human resources. The use of an accurate, economical, and quantifiable noninfectious viral surrogate would enable downstream purification scientists to study viral clearance throughout process development. This report explores the use of a BSL-1 compatible, noninfectious MVM particles to predict viral clearance results over…